Nationwide real-world data demonstrate favorable survival outcomes following adoption of dual anti-HER2 therapy. While these findings are broadly consistent with the CLEOPATRA trial, the observational design does not allow direct assessment of equivalence between studies.

P2, N=88, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Jun 2026 --> Jun 2027

Trastuzumab + pertuzumab (TP) was the most commonly used regimen in both neoadjuvant and adjuvant settings. The dual HER2 blockade regimens that were widely adopted in China for HR+/HER2+ early breast cancer have demonstrated effectiveness in improving pCR in routine clinical practice; a longer follow‑up is required to validate survival outcomes. None.

Ultrasensitive ctDNA analyses demonstrated high baseline detection rates and near-universal clearance after abbreviated neoadjuvant therapy, supporting further investigation of ctDNA-guided de-escalation strategies in this setting. ClinicalTrials.gov Identifier: NCT03716180.

P3, N=360, Suspended, National Cancer Institute (NCI) | Recruiting --> Suspended

In this Romanian single-center cohort, pCR was independently predicted by clinical subtype and a limited set of biological variables, in line with contemporary literature. Although baseline patient-reported outcomes did not improve prediction of pathological response, the high prevalence of pre-treatment anxiety and the emergence of clinical depression during NAC argue for systematic psychosocial screening as part of standard neoadjuvant care.

Neoadjuvant dual HER2 blockade with trastuzumab and pertuzumab plus chemotherapy represents the current standard-of-care for HER2-positive breast cancer. Importantly, Xenium in situ profiling further revealed biological correlates underlying model predictions, including HER2-enriched tumor cell aggregation and neutrophil-helper T-cell interactions, thereby highlighting the mechanistic interpretability of the model. Collectively, HER2-LADDER unites digital pathology and high-resolution spatial profiling into a clinically accessible AI framework, offering a robust, transparent, and biologically grounded tool to tailor individualized HER2-targeted therapy optimization.

P2, N=63, Completed, City of Hope Medical Center | Active, not recruiting --> Completed

Multimodal HER2 testing is needed to accurately identify candidates for HER2-targeted treatment, as NGS alone misses a significant proportion of cases. Patients who develop resistance to one anti-HER2 agent may still achieve benefit from subsequent HER2-directed regimens. Early and serial treatment with HER2-directed agents should be considered for patients with HER2 + GI cancers.

P2, N=702, Recruiting, West German Study Group | Active, not recruiting --> Recruiting | N=402 --> 702 | Trial completion date: Jun 2029 --> Sep 2030 | Trial primary completion date: Jun 2025 --> Jun 2030

Given the clinical severity, inpatient treatment was promptly initiated with trastuzumab and pertuzumab every three weeks, combined with weekly paclitaxel at a 50% dose reduction. In carefully selected patients, early and sustained HER2-directed therapy can lead to meaningful clinical recovery when options appear limited. Such cases help bridge the evidence gap for this high-risk group and may inform future therapeutic considerations.

Patient characteristics reflect current Chinese practice. Increasing adoption of diarrhoea prophylaxis in real-world practice reflects growing clinical experience with neratinib and its recognised benefit in preventing diarrhoea.